X-linked Opitz G/BBBsyndrome is a congenital midline malformation syndrome characterized by facialanomalies, laryngo-tracheo-esophageal defects, and genitourinary abnormalities.Facial anomalies seen in X-linked Opitz G/BBB syndrome include ocularhypertelorism, prominent forehead, widow's peak, broad nasal bridge, andanteverted nares. Genitourinary abnormalities include hypospadias,cryptorchidism, and hypoplastic/bifid scrotum. The condition is geneticallyheterogeneous, as there is an autosomal dominant form as well.
Hypertelorismand hypospadias are the most frequent manifestations of X-linked Opitz G/BBBsyndrome, being present in almost all individuals. Developmental delay andmental retardation are observed in about 50% of affected males. Cleft lip and/or palate are present in approximately 50% of affected individuals. Other malformations present in fewer than 50% of individualsinclude congenital heart defects, imperforate or ectopic anus, and midline brain defects(Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosumand/or cerebellar vermis). Monozygotic twinning is unusually frequent infamilies of individuals with X-linked Opitz G/BBB syndrome, and may be amanifestation of the defect; unusually severe cases with early lethality occuras twins. Wide clinical variability occurs even among members of the samefamily. Female carriers usually manifest only ocular hypertelorism. Theprevalence of X-linked Opitz G/BBB syndrome ranges from one in 50,000 to one in100,000 males.
Thediagnosis of X-linked Opitz G/BBB syndrome is established most often byclinical findings. MID1 (Xp22) is the only gene currently known to be associated with X-linked Opitz G/BBB syndrome. Sequence analysis of the MID1 gene detects mutations in15%-45% of males with clinically diagnosed Opitz G/BBB syndrome. Deletions andduplications in and of the MID1 genehave also been reported. The cohorts tested for MID1 mutations ofteninclude simplex cases (i.e., individuals with no family history of Opitz G/BBB syndrome), who therefore cannot be determined to have either theX-linked form or the autosomal dominant form. The detection rate is higher in individuals with clear X-linkedinheritance. De novo mutations havebeen reported.
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This test is indicated for:
- Confirmation of a clinical/biochemical diagnosis of X-linked Opitz G/BBB syndrome in individuals who have tested negative for sequence analysis
- Carrier testing in adult females with a family history of X-linked Opitz G/BBB syndrome who have tested negative for sequence analysis
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
- Sequencing analysis of the MID1 gene is available (ZC) and is required before deletion/duplication analysis.
- ACGH array-based test for deletion/duplication analysis of 64 differentX-linked intellectual disability genes is available (OL).
- Prenataltesting is available to adult females who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.